1. Field of the Invention
The invention relates to antimicrobial compositions for use in controlling the growth of microorganisms in the oral cavity and on dental prostheses. The antimicrobial compositions of the invention are useful as denture adhesives and as denture cleansing creams or soaking compositions. The invention also relates to methods for making and using such antimicrobial compositions.
2. Description of Related Art
Dentures and dental plates function as a substitute for missing teeth in the mouth. While dentures are usually carefully fitted for the user, the fit can change over time, causing discomfort and slippage. To alleviate the discomfort and to control the slippage, a denture adhesive may be applied to the denture. Denture adhesives usually comprise water swellable gums and/or polymers suspended in oils and petrolatum. The gums and/or polymers hydrate and become tacky when introduced to the saliva in the oral cavity, thus holding the dentures in place. Oils and petrolatum are traditionally used in the composition to avoid the premature washing away of the adhesive actives due to the constant flow of saliva through the oral cavity.
Candida albicans is one species of bacteria known to cause denture stomatitis, which is a serious infection of the oral mucosa. Denture stomatitis generally develops due to poor-fitting dentures or poor denture cleanliness. Normally, mucosal infections are not a problem since natural substances found in the saliva act to inhibit bacterial and fungal growth. Dentures however, are known to prevent saliva from getting to and contacting the mucosal surfaces beneath the denture. Without the presence of saliva to wash the mucosal surface under the denture, bacterial species such as C. albicans can flourish and cause disease.
To control bacterial growth, many different approaches have been tried. Dentifrices have been combined with antibacterial agents such as Triclosan, and mouthwashes and oral rinses, such as Listerine.RTM. mouthwash, advertise effectiveness in killing germs. Unfortunately, dentifrices and mouthwashes do not solve the problem of denture stomatitis. The dentures can still prevent saliva from reaching the oral mucosa during use, and C. albicans can still flourish.
Others have tried to incorporate antimicrobial agents into denture adhesives to inhibit growth of C. albicans and prevent stomatitis. Unfortunately, as shown below, many antimicrobial agents known to be effective against C. albicans have been tested and have failed to show any significant efficacy in a denture adhesive against C. albicans. Without wishing to be bound by theory, it appears that these antimicrobial agents may have been deactivated or sequestered in the matrix of the denture adhesive. There is still a strong need in the art for antimicrobial agents that can remain effective against C. albicans in a denture adhesive while retaining acceptable adhesive and organoleptic qualities.
Denture adhesive compositions and denture creams are well known in the art. U.S. Pat. No. 5,424,058 to Rajaiah et al., for example, discloses denture stabilizing compositions comprising the mixed partial salts of a lower alkyl vinyl ether/maleic acid copolymer (AVE/MA). U.S. Pat. No. 4,518,721 to Dhabhar et al. is directed to a hydrophilic denture adhesive consisting of sodium carboxymethyl cellulose and poly(oxy) ethylene oxide in a hydrophilic vehicle. The salts discussed in that patent include zinc and strontium. The AVE/MA copolymer is preferably combined with a second co-adhesive selected from the group consisting of natural gums, saccharide and cellulose derivatives and mixtures thereof. U.S. Pat. No. 5,395,867 to Prosise et al. is directed to denture adhesives with extended holding power comprising the mixed calcium, sodium, strontium, zinc, magnesium and potassium salts of the AVE/MA copolymer together with a non-cross linked non-ionic guar gum in an oil base carrier.
U.S. Pat. No. 5,369,145 to Gasman et al. teaches a denture adhesive composition comprising carboxymethyl cellulose and a partially neutralized sodium salt of AVE/MA copolymer that is further crosslinked with zinc and, optionally, other cations. The denture adhesive provides strong adhesion and bonding properties and is rapidly hydrated when applied in the oral cavity. Other denture adhesive compositions comprising mixed salts of a lower alkyl vinyl ether/maleic acid or maleic anhydride copolymers are disclosed in U.S. Pat. Nos. 5,304,616 to Rajaiah et al., 5,204,414 to Pelah et al., and 5,006,571 to Kumar et al. U.S. Pat. No. 4,470,814 to Chang also teaches a neutralized cross-linked polyacrylic acid and a hydrophilic polymer such as carboxymethyl cellulose or hydroxy propyl guar gum. None of these adhesives, however, are asserted to have antimicrobial or antibacterial properties.
Many efforts have been directed to antimicrobial compositions in the oral cavity. U.S. Pat. No. 5,403,579 to Michaels et al., for example, is directed to compositions for enhancing oral hygiene consisting of an antimicrobial compound comprising a higher alkyl-N-sulfobetaine together with a high alkyl N,N-dimethylamine oxide in a carrier base, which is formulated with other ingredients as an antiseptic mouthwash or toothpaste. These mouthwashes and toothpastes reduce plaque, calculus, bad breath and cavities.
U.S. Pat. No. 5,006,340 to Atsuta et al. is directed to a curable tooth restoration polymer that can act as a sustained release carrier for an antimicrobial agent. A polymerization initiator and other fillers react to harden and repair damaged enamel, and the polymer slowly releases the bactericidal agent to prevent or retard growth of microflora in the mouth.
The use of antimicrobial agents generally is well known. U.S. Pat. No. 4,766,113 to West et al., for example, discloses the use of copper hydrate together with 8-hydroxy quinoline as a broad spectrum antimicrobial agent in agricultural and mammalian veterinary applications and for human use as well. U.S. Pat. No. 4,694,000 to Timmerran et al. discloses biocidal quinzoline and isoquinoline derivatives including copper complexes thereof. U.S. Pat. Nos. 2,745,832 to Roth et al. and 2,769,006 to Kalberg disclose metal quinolates such as 8-hydroxy quinoline and copper, calcium and magnesium salts thereof as useful fungicidal actives.
One expired patent, U.S. Pat. No. 2,574,476 to Heath et al., discloses an antiseptic dental plate adhesive to control bacteria that cause bad breath. The adhesive comprises 8-hydroxy quinoline as the active antimicrobial in an oil and petrolatum base. U.S. Pat. No. 3,003,988 to Germann et al. also discloses the use of 8-hydroxyquinoline as an antibacterial agent in a denture adhesive.